Entropic and Enthalpic Contributions to Stereospecific Ligand Binding from Enhanced Sampling Methods
The stereoselective binding of R- and S-propranolol to the metabolic enzyme cytochrome P450 2D6 and its mutant F483A was studied using various computational approaches. Previously reported free-energy differences from Hamiltonian replica exchange simulations, combined with thermodynamic integration, are compared to the one-step perturbation approach, combined with local-elevation enhanced sampling, and an excellent agreement between methods was obtained. Further, the free-energy differences are interpreted in terms of enthalpic and entropic contributions where it is shown that exactly compensating contributions obscure a molecular interpretation of differences in the affinity while various reduced terms allow a more detailed analysis, which agree with heuristic observations on the interactions.
|Título según WOS:||Entropic and Enthalpic Contributions to Stereospecific Ligand Binding from Enhanced Sampling Methods|
|Título según SCOPUS:||Entropic and enthalpic contributions to stereospecific ligand binding from enhanced sampling methods|
|Título de la Revista:||JOURNAL OF CHEMICAL INFORMATION AND MODELING|
|Editorial:||AMER CHEMICAL SOC|
|Fecha de publicación:||2014|
|Página de inicio:||151|